CN113476608A - A pharmaceutical composition for treating cancer - Google Patents
A pharmaceutical composition for treating cancer Download PDFInfo
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- CN113476608A CN113476608A CN202110853868.6A CN202110853868A CN113476608A CN 113476608 A CN113476608 A CN 113476608A CN 202110853868 A CN202110853868 A CN 202110853868A CN 113476608 A CN113476608 A CN 113476608A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The invention provides a combined medicament for treating cancer. Belongs to the technical field of medicines and comprises a PARP1 inhibitor and a FOXM1 inhibitor. The two inhibitors have the limitations of narrow indication, easy generation of drug resistance and the like when being used for treating tumors independently. The pharmaceutical composition can obtain very strong anti-tumor effect according to effective administration dosage and administration mode, and shows good synergistic effect. Particularly, the pharmaceutical composition of the invention shows stronger effect than that of a single drug in the inhibition of the growth of tumors such as triple negative breast cancer, pancreatic cancer and the like, and provides a new way for tumor treatment.
Description
Technical Field
The invention belongs to the technical field of medicines, relates to a combined medicine for treating cancer, and particularly relates to a pharmaceutical composition taking a PARP1 inhibitor and a FOXM1 inhibitor as active ingredients, a preparation method thereof and application thereof in treating cancer.
Background
With the change of life style of people, the incidence of tumors is higher and higher, and the life health of human beings is seriously threatened. Currently, the incidence of breast cancer is the first place, and is one of the most common cancers in women threatening the world. Triple negative breast cancer is a highly heterogeneous tumor, and accounts for 15% -20% of breast cancer pathological subtypes. Because estrogen receptor, progestogen receptor and human epidermal growth factor receptor 2 are not expressed, triple negative breast cancer can not be treated in a targeted way by endocrine and other modes, and is a breast cancer subtype which is difficult to treat. The cytotoxic drugs such as paclitaxel, cisplatin and the like have obvious effect on treating early triple negative breast cancer, but have poor effect on treating late triple negative breast cancer. Pancreatic cancer is one of the most malignant digestive tract tumors, with an overall 5-year survival rate of less than 8%. Although a number of treatment regimens have been proposed, the prognosis for patients with pancreatic cancer has not improved significantly. Therefore, there is a need to find new strategies for treating a variety of cancers, including triple negative breast cancer, pancreatic cancer.
PARPs are signaling molecules and transduction proteins in response to DNA damage and are expressed abnormally in a variety of tumors. The PARPs enzyme family is NAD+As substrates, various cellular responses are regulated by the transfer of one or more ADP-ribose units to a receptor protein or itself. PARP1 and PARP2, which catalyze poly-ADP nuclear glycation, have been extensively studied and have been shown to be involved in regulating the base excision repair pathway of DNA single strand damage. Genes such as BRCA1/2 and Rad51 regulate and control damaged DNA double chains to carry out accurate repair through Homologous Recombination (HR) and other approaches. BRCA1/2 is easy to mutate, and the mutant BRCA1/2 can block a homologous recombination repair pathway, so that chromosome in cells is unstable; the BRCA1/2 mutation exists in various cancer tissues including triple negative breast cancer, ovarian cancer, prostatic cancer, pancreatic cancer and the like; restraining deviceThe expression and activity of PARP1/2 in such cancer cells can result in death of damaged DNA within the cell by failure of HR pathway repair. Based on the theory of "synthetic lethality", several PARP inhibitors, represented by olaparib, are marketed sequentially and are widely used to treat a variety of cancers that are deficient in HR repair. However, many PARP inhibitors, including olaparib, have the limitations of narrow indications and susceptibility to drug resistance.
FOXM1 is a transcription factor of the forkhead box family, also known as HFH-11, MPP-1 and WIN, with an evolutionarily conserved "wing-helix" DNA binding domain in this family. FOXM1 has G for regulating cell cycle1(ii) S and G2The transformation of/M, maintenance of mitotic spindle integrity, angiogenesis, metastasis, apoptosis, DNA damage repair, and tissue regeneration. FOXM1 has been shown to be over-expressed in breast cancer, pancreatic cancer, liver cancer and other tumors, and is closely involved in the processes of malignant proliferation, invasion and metastasis, chemotherapy drug resistance and the like of tumors. FDI-6 (3-amino-N- (4-fluorophenyl) -6- (thiophen-2-yl) -4- (trifluoromethyl) thieno [2,3-b]Pyridine-2-carboxamide, CAS No. 313380-27-7) is a specific inhibitor of FOXM1, and can regulate tumor cell cycle progression, DNA damage repair pathway, etc. to exert an antitumor effect by inhibiting the function of FOXM 1. As an important factor for regulating DNA damage repair, the FOXM1 and PARP1 are jointly inhibited from expressing and functioning, malignant proliferation of tumor cells can be better inhibited, and the gene is a novel strategy for targeted treatment of cancers such as breast cancer, pancreatic cancer and the like.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to provide a pharmaceutical composition with synergistic effect for treating tumors.
The technical scheme is as follows: the combined medicine for treating the cancer consists of a pharmaceutical active ingredient and a pharmaceutically acceptable carrier, wherein the pharmaceutical active ingredient contains a PARP1 inhibitor or a pharmaceutically acceptable salt thereof and a FOXM1 inhibitor or a pharmaceutically acceptable salt thereof.
Further, the PARP1 inhibitor is an artificially designed and synthesized compound, and the FOXM1 inhibitor is a compound inhibiting the function of the transcription factor FOXM 1.
Further, the PARP1 inhibitor is olaparib, rucapanib, nilapanib, tarapanib, fluxaparib, pamidrarib and verapamil or a pharmaceutically acceptable salt thereof.
Further, the FOXM1 inhibitor is FDI-6 and thiostrepton or a pharmaceutically acceptable salt thereof.
Further, the PARP1 inhibitor is Olaparib and the FOXM1 inhibitor is FDI-6.
Furthermore, the single use dose of the PARP1 inhibitor is 0.1-50 mg/kg, and the single use dose of the FOXM1 inhibitor is 0.1-50 mg/kg.
Furthermore, the single use dosage of the olaparib is 0.5-20 mg/kg, and the single use dosage of the FDI-6 is 0.5-20 mg/kg.
Further, the single use dosage of the olaparib is 1-10 mg/kg, and the single use dosage of the FDI-6 is 1-10 mg/kg.
Further, the cancer is a solid tumor of middle and advanced stage or a hematologic tumor.
Further, the cancer is triple negative breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, primary peritoneal cancer, prostate cancer, pancreatic cancer, and colon cancer.
Has the advantages that: compared with the prior art, the pharmaceutical composition can obtain very strong anti-tumor effect according to the effective administration dose and the administration mode, and shows better synergistic effect. Particularly, the pharmaceutical composition of the invention shows stronger effect than that of a single drug in the inhibition of the growth of tumors such as triple negative breast cancer, pancreatic cancer and the like, and provides a new way for tumor treatment.
Drawings
FIG. 1 is a graph of the synergistic inhibition of proliferation of triple negative breast and pancreatic cancers in vitro by Olaparib and FDI-6 in accordance with the present invention; wherein CI < 1.0;
FIG. 2 is a schematic diagram of a clone formation experiment in the present invention;
FIG. 3 is a schematic diagram of the apoptosis assay of the present invention;
FIG. 4 is a graphical representation of the in vivo anti-tumor effect of Olaparib and/or FDI-6 of the present invention;
FIG. 5 is a statistical plot of tumor volume and body weight in Olaparib and/or FDI-6 of the present invention.
Detailed Description
The invention is further described below with reference to the accompanying drawings. The following examples are only for illustrating the technical solutions of the present invention more clearly, and the protection scope of the present invention is not limited thereby.
The combined medicine for treating the cancer consists of a pharmaceutical active ingredient and a pharmaceutically acceptable carrier, wherein the pharmaceutical active ingredient contains a PARP1 inhibitor or a pharmaceutically acceptable salt thereof and a FOXM1 inhibitor or a pharmaceutically acceptable salt thereof.
Further, the PARP1 inhibitor is an artificially designed and synthesized compound, and the FOXM1 inhibitor is a compound inhibiting the function of the transcription factor FOXM 1.
Further, the PARP1 inhibitor is Olaparib (Olaparib), lucapanib (rucapanib), nilapanib (Niraparib), Talazoparib (Talazoparib), Fluzoparib (Fluzoparib), Pamiparib (pamiaparib) and verapamil (Veliparib) or a pharmaceutically acceptable salt thereof.
Further, the FOXM1 inhibitor is FDI-6 (3-amino-N- (4-fluorophenyl) -6- (thiophen-2-yl) -4- (trifluoromethyl) thieno [2,3-b ] pyridine-2-carboxamide) and Thiostrepton (Thiostrepton) or a pharmaceutically acceptable salt thereof.
Further, the PARP1 inhibitor is Olaparib and the FOXM1 inhibitor is FDI-6.
Furthermore, the single use dose of the PARP1 inhibitor is 0.1-50 mg/kg, and the single use dose of the FOXM1 inhibitor is 0.1-50 mg/kg.
Further, the single-use dosage of the olaparib is 0.5-20 mg/kg, preferably 1-10 mg/kg;
the single-use dosage of the FDI-6 is 0.5-20 mg/kg, preferably 1-10 mg/kg.
Further, the cancer is a solid tumor of middle and advanced stage or a hematologic tumor.
Further, the cancer is triple negative breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, primary peritoneal cancer, prostate cancer, pancreatic cancer, colon cancer and the like.
The pharmaceutical composition can be prepared into various preparations. Such as common tablet, capsule, sustained release tablet, sustained release capsule, dispersible tablet, chewable tablet, orally disintegrating tablet, dripping pill, liposome, solid dispersion, liquid preparation, etc.
Pharmacodynamic tests prove that the pharmaceutical composition can be used for treating various cancers, and the combined use of the PARP1 inhibitor and the FOXM1 inhibitor has synergistic effect on curative effect, and the curative effect is better than that of the PARP1 inhibitor alone or the FOXM1 inhibitor alone.
The following are some pharmacodynamic tests and results of the pharmaceutical composition of the present invention, in which the PARP1 inhibitor used in the test was olaparib, and the FOXM1 inhibitor used in the test was FDI-6; the combined use of other PARP1 inhibitors or pharmaceutically acceptable salts thereof and FOXM1 inhibitors or pharmaceutically acceptable salts thereof has the same therapeutic effect.
The present invention is described in further detail below by way of specific examples, but it should not be construed that the orientation of the above-described subject matter of the present invention is limited to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Materials and reagents in the examples: triple negative breast cancer cell line MDA-MB-231, pancreatic cancer cell line SW1990, L-15 medium and 10% fetal bovine serum (Bio-Channel) in 5% CO2Culturing at 37 deg.C; olaparib and FDI-6(MedChemexpress) were dissolved in DMSO. Apoptosis detection kit (KeyGEN), crystal violet staining solution (KeyGEN).
The experimental operation steps are as follows:
MTT assay cell proliferation:
cells were seeded in 96-well plates at 3000-2Culturing at 37 deg.C for 24 hr, and treating with corresponding medicine for 7 daysAdding thiazole blue dye (MTT) to incubate for 3-4h, discarding the culture medium, adding DMSO to fully dissolve and mix uniformly, and detecting cell proliferation. Cell growth inhibition ═ (1-absorbance of experimental/control) × 100%.
Clone formation experiments:
inoculating the cells into a 24-well plate at 800-; after fixing with 4% paraformaldehyde for 15 minutes, the plate was stained with 0.1% crystal violet stain for 10 minutes, and photographed by observation with an inverted fluorescence microscope.
Apoptosis assay:
inoculating the cells into a 35mm culture dish at a density of 30-50% of each dish, culturing overnight to allow the cells to adhere to the wall, and then adding corresponding drugs for treatment for 7 days; the cells were digested with pancreatin and washed twice with PBS; cells were then stained with propidium iodide and annexin V-FITC and, after completion, analyzed for apoptosis using a Meitian and whirlpool MACSQurant flow cytometer.
The statistical analysis method comprises the following steps: statistical analysis is carried out by adopting SPSS19.0 software; the measured data are expressed in x + -s, two groups of comparison are tested by Student's t, a plurality of groups of comparison are analyzed by one-factor variance, and two groups of comparison are tested by LSD.*P＜0.05、#P < 0.05 is statistically significant.
Example 1PARP1 inhibitor in combination with FOXM1 inhibitor inhibited triple negative breast and pancreatic cancer cell growth in vitro:
1. the experimental method comprises the following steps:
(1) MTT detection cell proliferation:
treating two tumor cells with DMSO (control), Olaparib, FDI-6 and Olaparib and FDI-6 in a combined way, wherein the molar ratio of Olaparib to FDI-6 in the combined treatment group is 1 (0.5-2); after 7 days, cell proliferation was detected with MTT;
(2) cloning experiments to detect cell number:
the effect of the combination drug on cell proliferation was examined using a clonogenic assay, Olaparib in combination with FDI-6 treatment of two tumor cells (MDA-MB-231 Olaparib 2.0. mu.M, FDI-62.0. mu.M; SW1990 Olaparib 3.0. mu.M, FDI-63.0. mu.M); after 10 days, fixing with 4% paraformaldehyde for 15min, dyeing with crystal violet for 10min, and taking pictures by observing with an inverted fluorescence microscope;
(3) and observing cell apoptosis:
after MDA-MB-231 cells were treated with Olaparib 4.0. mu.M in combination with FDI-64.0. mu.M for 7 days, apoptosis was detected by flow cytometry; SW1990 (Olaparib 3.0. mu.M, FDI-63.0. mu.M) treatment with MDA-MB-231 detected apoptosis.
2. The experimental results are as follows:
(1) calculating a synergy index CI by using a Chou-Talalay formula according to the result of MTT cell proliferation, wherein CI <1.0 represents synergistic effect, CI ═ 1.0 represents only additive effect, and CI >1.0 represents antagonistic effect;
as shown in FIG. 1, the molar ratio of Olaparib and FDI-6 is in the range of 1 (0.5-2), and the CI values in the two tumor cells are less than 1, which indicates that the Olaparib and FDI-6 can synergistically inhibit the growth of the tumor cells in the determined molar ratio range;
(2) cell clone number:
after Olaparib and FDI-6 combined treatment of triple negative breast cancer cells MDA-MB-231 and pancreatic cancer cells SW1990 at a 1:1 molar ratio, the number of cell clones was significantly less than the groups using Olaparib or FDI-6 alone, see FIG. 2; further verifies the long-term effect of Olaparib combined with FDI-6 on the survival of tumor cells;
(3) and apoptosis:
apoptosis data analysis shows that compared with a single drug group, the combined treatment group of Olaparib and FDI-6 (molar ratio 1:1) can remarkably promote apoptosis of MDA-MB-231 cells and SW1990 cells, and the figure is 3;
the experimental result shows that the Olaparib and the FDI-6 have excellent synergistic anti-tumor effect.
Example 2 Olaparib in combination with FDI-6 inhibits the growth of triple negative breast cancer xenograft tumors in vivo
(1) And the tested medicine:
PARP inhibitors: olaparib; FOXM1 inhibitor: FDI-6;
the preparation method comprises the following steps: olaparib was formulated with 10% DMSO and 10% beta cyclodextrin; FDI-6 used 10%
Preparing DMSO, 10% Tween and 10% beta cyclodextrin;
(2) and experimental animals:
BALB/cA-nude mice, 6-8 weeks, female; a breeding environment: an SPF level;
(3) and an experiment step:
inoculating MDA-MB-231 cells of human triple negative breast cancer into nude mice subcutaneously respectively until the tumor grows to 100-3Then, the animals were randomly divided into a control group, an olaparib group, an FDI-6 group and a combined administration group; olaparib group was injected intraperitoneally with Olaparib (60mg/kg), once daily; FDI-6 group is administered by intraperitoneal injection of FDI-6(60mg/kg) once a day; the combination group was intraperitoneally injected with Olaparib (30mg/kg) and FDI-6(30mg/kg) (generally, the molar ratio of Olaparib to FDI-6 was approximately 1: 1; not limited to this molar ratio; DI-6 molecular weight 437.434; Olaparib molecular weight 434.46; Olaparib/FDI-6 ═ 1:1.006), once a day; the volume of the transplanted tumor was measured every two days, the mice were weighed, the data recorded, and the animals were sacrificed on day 28;
(4) and the experimental result is as follows:
the results show that tumor growth was significantly inhibited in the Olaparib and FDI-6 groups alone compared to the model group. The combined drug group tumors were significantly reduced in both weight and volume compared to the single drug group and the model group (fig. 4, fig. 5).
The combined group has stronger inhibiting effect on triple negative breast cancer cell MDA-MB-231 xenograft tumor than the Olaparib single group or the FDI-6 single group, and the difference is obvious, which shows that the Olaparib and the FDI-6 can play better anti-tumor effect in vivo.
In conclusion, the combined medicament disclosed by the invention can obviously inhibit the growth of tumor cells in vivo and in vitro, and has a good clinical application prospect.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (10)
1. A combination drug for treating cancer, which consists of a pharmaceutical active ingredient and a pharmaceutically acceptable carrier, wherein the pharmaceutical active ingredient contains a PARP1 inhibitor or a pharmaceutically acceptable salt thereof and a FOXM1 inhibitor or a pharmaceutically acceptable salt thereof.
2. The combination of claim 1, wherein the PARP1 inhibitor is an artificially designed compound and the FOXM1 inhibitor is a compound that inhibits the function of the transcription factor FOXM 1.
3. The combination of claim 1, wherein the PARP1 inhibitor is Olaparib, Rukaparib, Nilaparib, Tallaparib, Fluzoparib, Pamiparib, and verapamil, or a pharmaceutically acceptable salt thereof.
4. The combination of claim 1, wherein the FOXM1 inhibitor is FDI-6 and thiostrepton or a pharmaceutically acceptable salt thereof.
5. A combination for use in the treatment of cancer according to claims 3 and 4, wherein the PARP1 inhibitor is Olaparib and the FOXM1 inhibitor is FDI-6.
6. The combination of claim 1, wherein the single use dose of the PARP1 inhibitor is 0.1-50 mg/kg and the single use dose of the FOXM1 inhibitor is 0.1-50 mg/kg.
7. The combination as claimed in claim 5, wherein the single use dose of olaparib is 0.5-20 mg/kg, and the single use dose of FDI-6 is 0.5-20 mg/kg.
8. The combination as claimed in claim 5, wherein the single use dose of olaparib is 1-10 mg/kg, and the single use dose of FDI-6 is 1-10 mg/kg.
9. The combination according to claim 1, wherein the cancer is a solid tumor of intermediate or advanced stage or a hematological tumor.
10. A combination for use in the treatment of cancer according to claims 1 and 9, wherein the cancer is triple negative breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, primary peritoneal cancer, prostate cancer, pancreatic cancer and colon cancer.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112218845A (en) * | 2018-04-10 | 2021-01-12 | 伊利诺伊大学理事会 | FOXM1 inhibitor compositions and methods of use thereof |
| CN115105539A (en) * | 2022-08-01 | 2022-09-27 | 大连医科大学附属第二医院 | PARP inhibitor and Chinese sage herb combined breast cancer treatment and pharmaceutical composition |
| CN116019814A (en) * | 2022-09-08 | 2023-04-28 | 北京大学 | Application of IRAK1 inhibitor combined with PARP inhibitor in preparation of antitumor medicament |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101999002A (en) * | 2008-02-04 | 2011-03-30 | 彼帕科学公司 | Methods of diagnosing and treating PARP-mediated diseases |
| US20200048716A1 (en) * | 2017-11-03 | 2020-02-13 | Twister Biotech, Inc | Using minivectors to treat ovarian cancer |
| CN111671902A (en) * | 2020-03-19 | 2020-09-18 | 中山大学孙逸仙纪念医院 | Sensitizer drug, drug composition and application |
| CN112546066A (en) * | 2020-12-21 | 2021-03-26 | 中国科学院物理研究所 | Anticancer composition, combination product, preparation method and application thereof |
-
2021
- 2021-07-27 CN CN202110853868.6A patent/CN113476608A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101999002A (en) * | 2008-02-04 | 2011-03-30 | 彼帕科学公司 | Methods of diagnosing and treating PARP-mediated diseases |
| US20200048716A1 (en) * | 2017-11-03 | 2020-02-13 | Twister Biotech, Inc | Using minivectors to treat ovarian cancer |
| CN111671902A (en) * | 2020-03-19 | 2020-09-18 | 中山大学孙逸仙纪念医院 | Sensitizer drug, drug composition and application |
| CN112546066A (en) * | 2020-12-21 | 2021-03-26 | 中国科学院物理研究所 | Anticancer composition, combination product, preparation method and application thereof |
Non-Patent Citations (4)
| Title |
|---|
| KARAN ULHAKA等: "The Anticancer Effects of FDI-6, a FOXM1 Inhibitor, on Triple Negative Breast Cancer", 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》 * |
| PINGPING FANG等: "Olaparib-induced Adaptive Response Is Disrupted by FOXM1 Targeting that Enhances Sensitivity to PARP Inhibition", 《MOL CANCER RES.》 * |
| YU LI等: "BKM120 sensitizes BRCA‑proficient triple negative breast cancer cells to olaparib through regulating FOXM1 and Exo1 expression", 《SCIENTIFIC REPORTS》 * |
| 陆毅等: "PARP抑制剂奥拉帕尼的专利分析", 《中国新药杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112218845A (en) * | 2018-04-10 | 2021-01-12 | 伊利诺伊大学理事会 | FOXM1 inhibitor compositions and methods of use thereof |
| CN115105539A (en) * | 2022-08-01 | 2022-09-27 | 大连医科大学附属第二医院 | PARP inhibitor and Chinese sage herb combined breast cancer treatment and pharmaceutical composition |
| CN116019814A (en) * | 2022-09-08 | 2023-04-28 | 北京大学 | Application of IRAK1 inhibitor combined with PARP inhibitor in preparation of antitumor medicament |
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